Inhibition of endothelial interleukin-8 production and neutrophil transmigration by Staphylococcus aureus beta-hemolysin.
Neutrophils play a crucial role in the host response to infection with Staphylococcus aureus, which is a major human pathogen capable of causing life-threatening disease. Interleukin-8 (IL-8) is a potent chemoattractant and activator of neutrophils. We previously reported that S. aureus secretes a factor that suppresses IL-8 production by human endothelial cells. Here we isolated an inhibitor of IL-8 production from the supernatant and identified it as staphylococcal beta-hemolysin. Beta-hemolysin reduced IL-8 production without cytotoxicity to endothelial cells. Pretreatment with beta-hemolysin decreased the expression of both IL-8 mRNA and protein induced by tumor necrosis factor alpha (TNF-alpha). Migration of neutrophils across TNF-alpha-activated endothelium was also inhibited by beta-hemolysin. In contrast, beta-hemolysin had no effect on intercellular adhesive molecule 1 expression in activated endothelial cells. These results showed that beta-hemolysin produced by S. aureus interferes with inflammatory signaling in endothelial cells and may help S. aureus evade the host immune response.
Tajima
Akiko
A
Department of Bacteriology, Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan. tajima@jikei.ac.jp
Iwase
Tadayuki
T
Shinji
Hitomi
H
Seki
Keiko
K
Mizunoe
Yoshimitsu
Y
D001427:Bacterial Toxins / Q000633:toxicity*; D054441:Cell Migration Assays, Leukocyte; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000382:microbiology*; D006460:Hemolysin Proteins / Q000633:toxicity*; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors*; D009504:Neutrophils / Q000276:immunology*; D013108:Sphingomyelin Phosphodiesterase / Q000633:toxicity*; D013211:Staphylococcus aureus / Q000276:immunology*
D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D016209:Interleukin-8; D013108:Sphingomyelin Phosphodiesterase; C029878:hlb protein, Staphylococcus aureus